Source:http://linkedlifedata.com/resource/pubmed/id/16292653
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2006-1-9
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pubmed:abstractText |
The anti-inflammatory/immunoparalytic phase of the systemic inflammatory response syndrome (SIRS) following major insult (surgery, thermal/traumatic injury) is of major clinical importance in the neonate, during which the risk of infection is particularly great. Here, the mechanisms by which TNF-alpha production is suppressed in response to infection are largely unknown. We questioned whether TNF-alpha itself could be a critical mediator of this suppression. Monocytes, isolated from cord blood (n=3), were treated with LPS (100 ng/ml), TNF-alpha (10 ng/ml, +/- anti-TNF-alpha antibody) for 18 and 36 h. Cells were then restimulated with LPS (Gram -ve) or Pam-3-Cys (Gram +ve) for 24 h. This was also done in the presence of selective inhibitors of MAP kinases p38, MEK and JNK. TNF-alpha, IL-6, IL-10 and IL-8 were quantified by ELISA CD86 and HLA-DR expression were determined flow cytometrically. Cells stimulated with LPS for 24 h produced TNF-alpha (282 pg/ml), IL-10 (1,236 pg/ml), IL-6 (2,694 pg/ml) and IL-8 (2,144 pg/ml). In cells pre-exposed to TNF-alpha for 36 h, there was a significant suppression in TNF-alpha and IL-6 levels (9 and 221 pg/ml, respectively) (P<0.05) with minimal impact on IL-10 (1,206 pg/ml) and IL-8 levels (1,886 pg/ml). A similar effect was seen with Pam-3-Cys with a tenfold decrease in levels of TNF-alpha and IL-6 (86-->8.5 pg/ml and 458-->46 pg/ml, respectively) with no effect on IL-10 and IL-8 levels. Anti-TNF-alpha antibody negated this effect. Inhibition of p38 kinase reversed the TNF-alpha effect. Inhibition of the JNK and MEK kinases had no effect. A reduction in the expression of CD86 and HLA-DR was observed. This ex-vivo model of non-septic SIRS demonstrates that TNF-alpha, released during a major insult, can suppress subsequent monocyte responses to bacterial agents through p38 MAP kinase, making it a potential therapeutic target.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/N-palmitoyl-S-(2,3-bis(palmitoyloxy)...,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0179-0358
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
22
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
24-30
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16292653-Cytokines,
pubmed-meshheading:16292653-Fetal Blood,
pubmed-meshheading:16292653-Humans,
pubmed-meshheading:16292653-Immune Tolerance,
pubmed-meshheading:16292653-Infant, Newborn,
pubmed-meshheading:16292653-Lipopolysaccharides,
pubmed-meshheading:16292653-Lipoproteins,
pubmed-meshheading:16292653-Monocytes,
pubmed-meshheading:16292653-Statistics, Nonparametric,
pubmed-meshheading:16292653-Systemic Inflammatory Response Syndrome,
pubmed-meshheading:16292653-Tumor Necrosis Factor-alpha,
pubmed-meshheading:16292653-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2006
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pubmed:articleTitle |
TNF-alpha is a mediator of the anti-inflammatory response in a human neonatal model of the non-septic shock syndrome.
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pubmed:affiliation |
The Children's Research Centre, Our Lady's Hospital for Sick Children, Dublin, Ireland. sineadhassett@hotmail.com
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pubmed:publicationType |
Journal Article,
In Vitro
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